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Cationic Photosensitizer-Functionalized Bacteria for Targeted Photothermal-Photodynamic Therapy with Immune
Ling Lei1, Junyi Liu1, Yang Liu1
1State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
Journal of Medicinal Chemistry
|June 2, 2026
Summary
Engineered bacteria coated with a cationic photosensitizer (VNP@Cy-HEX) effectively target tumors. This hybrid therapy combines photothermal and photodynamic effects, significantly inhibiting solid tumor growth and enhancing anti-tumor immunity.
Area of Science:
- Biomedical Engineering
- Cancer Therapy
- Immunology
Background:
- Bacteria have natural tumor-targeting and immune-stimulating abilities but limited efficacy alone.
- Developing strategies to enhance bacterial tumor accumulation and therapeutic output is crucial for cancer treatment.
Purpose of the Study:
- To engineer bacteria with enhanced tumor tropism and photo-immune therapeutic efficacy.
- To create a bacteria-photosensitizer hybrid (VNP@Cy-HEX) for combined photothermal and photodynamic therapy.
Main Methods:
- Bacteria were modified with a tricationic heptamethine photosensitizer (Cy-HEX) to form VNP@Cy-HEX.
- The hybrid's tumor accumulation was assessed via motility and hypoxia-directed localization.
- Photothermal and photodynamic properties of Cy-HEX were evaluated under near-infrared irradiation.
- Immunogenic cell death, dendritic cell maturation, and T-cell activation were analyzed post-treatment.
Main Results:
- Tricationic modification improved bacterial adhesion, solubility, and tumor accumulation.
- VNP@Cy-HEX exhibited efficient photothermal conversion (η = 54.9%) and photostability.
- The treatment induced immunogenic cell death, enhanced immune cell activity, and achieved significant tumor regression (94.4% inhibition in vivo).
Conclusions:
- Cationic photosensitizer functionalization enhances bacterial tumor targeting and photo-immune therapeutic outcomes.
- VNP@Cy-HEX offers a promising chemically guided strategy for bacteria-based cancer therapy.
- This approach leverages bacterial properties with photosensitizer technology for improved cancer treatment efficacy.
